title: Factors affecting the infant antibody response to measles immunisation in Entebbe-Uganda.
abstract: BACKGROUND
  Vaccine failure is an important concern in the tropics with many contributing elements. Among them, it has been suggested that exposure to natural infections might contribute to vaccine failure and recurrent disease outbreaks. We tested this hypothesis by examining the influence of co-infections on maternal and infant measles-specific IgG levels.
  
  
  METHODS
  We conducted an observational analysis using samples and data that had been collected during a larger randomised controlled trial, the Entebbe Mother and Baby Study (ISRCTN32849447). For the present study, 711 pregnant women and their offspring were considered. Helminth infections including hookworm, Schistosoma mansoni and Mansonella perstans, along with HIV, malaria, and other potential confounding factors were determined in mothers during pregnancy and in their infants at age one year. Infants received their measles immunisation at age nine months. Levels of total IgG against measles were measured in mothers during pregnancy and at delivery, as well as in cord blood and from infants at age one year.
  
  
  RESULTS
  Among the 711 pregnant women studied, 66% had at least one helminth infection at enrolment, 41% had hookworm, 20% M. perstans and 19% S. mansoni. Asymptomatic malaria and HIV prevalence was 8% and 10% respectively. At enrolment, 96% of the women had measles-specific IgG levels considered protective (median 4274 mIU/ml (IQR 1784, 7767)). IgG levels in cord blood were positively correlated to maternal measles-specific IgG levels at delivery (r = 0.81, p < 0.0001). Among the infants at one year of age, median measles-specific IgG levels were markedly lower than in maternal and cord blood (median 370 mIU/ml (IQR 198, 656) p < 0.0001). In addition, only 75% of the infants had measles-specific IgG levels considered to be protective. In a multivariate regression analysis, factors associated with reduced measles-specific antibody levels in infancy were maternal malaria infection, infant malaria parasitaemia, infant HIV and infant wasting. There was no association with maternal helminth infection.
  
  
  CONCLUSIONS
  Malaria and HIV infection in mothers during pregnancy, and in their infants, along with infant malnutrition, may result in reduction of the antibody response to measles immunisation in infancy. This re-emphasises the importance of malaria and HIV control, and support for infant nutrition, as these interventions may have benefits for vaccine efficacy in tropical settings.
authors.affiliation: Co-infection Studies Programme, MRC/UVRI Uganda Research Unit on AIDS, Uganda Virus Research Institute, PO BOX 49, Entebbe, Uganda. dennison.kizito@mrcuganda.org
authors.forename: Dennison
authors.initials: D
authors.lastname: Kizito
authors.forename: Robert
authors.initials: R
authors.lastname: Tweyongyere
authors.forename: Alice
authors.initials: A
authors.lastname: Namatovu
authors.forename: Emily L
authors.initials: EL
authors.lastname: Webb
authors.forename: Lawrence
authors.initials: L
authors.lastname: Muhangi
authors.forename: Swaib A
authors.initials: SA
authors.lastname: Lule
authors.forename: Henry
authors.initials: H
authors.lastname: Bukenya
authors.forename: Stephen
authors.initials: S
authors.lastname: Cose
authors.forename: Alison M
authors.initials: AM
authors.lastname: Elliott
mesh_terms: D000328:Adult; D000818:Animals; D000917:Antibody Formation; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D007231:Infant, Newborn; D007411:Intestinal Diseases, Parasitic / Q000150:complications / Q000276:immunology*; D008288:Malaria / Q000150:complications / Q000276:immunology*; D008297:Male; D008457:Measles / Q000276:immunology / Q000517:prevention & control; D008458:Measles Vaccine / Q000008:administration & dosage / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D013048:Specimen Handling; D014454:Uganda / Q000453:epidemiology
chemical_list: D007074:Immunoglobulin G; D008458:Measles Vaccine